This project will investigate the role the respiratory chain and HCO3, CO2 and H ion play in modulating myocardial mechanical performance under both normoxic and hypoxic conditions. This study is based on the following hypotheses: A. The heart possesses an O2 sensor which decreases contractile performance prior to anoxia. B. The response of this sensor is in part determined by redox state of the respiratory chain and by the combined effects of H ion, HCO3 and CO2 and C. These messengers affect performance by altering the characteristics of Ca ions uptake and release by mitochondria and sarcoplasmic reticulum. These hypotheses are based on the following: 1. Of the intracellular parameters, only the respiratory chain redox state changes with the same time course are the observed mechanical dysfunction induced by hypoxia. 2. The presence of HCO3/CO2 modified myocardial response to (H ion), 3. Changes in any two of the dependent variables - (H ion), (HCO3 or PCO2 - affects the response to and recovery from hypoxia and 4. By prevalence, location and capability, mitochondria must be considered, a priori, to play an important role in performing this protective function. This project will concurrently study the response of isolated rabbit septa, isolated mitochondria and SR vesicles to changes in (H ion), (HCO3) and PCO2. Because this study is concerned with the early dynamic changes, non-invasive, optimal methods will be used to continuously measure the redox state of the respiratory chain, intracellular (H ion) and PO2. This study will concentrate on delineating the effects of HCO3 from those of (H ion) in the isolated organelles and the intact tissue. This project is designed to answer two questions: 1. What role do HCO3 and CO2 play in determining the effects of H ion on isolated organelle Ca ions uptake and release and 2. How do changes in (HCO3), PCO2 and (H ion) affect the functional relation between mechanical performance and oxygen availability in the intact tissue. Answering these is a necessary first step in testing the hypotheses outlined in the paragraph above and will provide valuable new insights into the basic mechanisms responsible for regulating myocardial performance.